Predictor Of Poor Recurrence-free Survival Research Articles

CXCR4 Expression as a Prognostic Biomarker in Soft Tissue Sarcomas.

Poor long-term survival in localized high-risk soft tissue sarcomas (STSs) of the extremities and trunk highlights the need to identify new prognostic factors. CXCR4 is a chemokine receptor involved in tumor progression, angiogenesis, and metastasis. The aim of this study was to evaluate the association between CXCR4 expression in tumor tissue and survival in STSs patients treated with neoadjuvant therapy. CXCR4 expression was retrospectively determined by immunohistochemical analysis in serial specimens including initial biopsies, tumors post-neoadjuvant treatment, and tumors after relapse. We found that a positive cytoplasmatic expression of CXCR4 in tumors after neoadjuvant treatment was a predictor of poor recurrence-free survival (RFS) (p = 0.003) and overall survival (p = 0.019) in synovial sarcomas. We also found that positive nuclear CXCR4 expression in the initial biopsies was associated with poor RFS (p = 0.022) in undifferentiated pleomorphic sarcomas. In conclusion, our study adds to the evidence that CXCR4 expression in tumor tissue is a promising prognostic factor for STSs.

ASAP1 Expression in Invasive Breast Cancer and Its Prognostic Role.

Breast cancer is a major global health burden with high morbidity and mortality rates. Previous studies have reported that increased expression of ASAP1 is associated with poor prognosis in various types of cancer. This study was conducted on 452 breast cancer patients who underwent surgery at Hanyang University Hospital, Seoul, South Korea. Data on clinicopathological characteristics including molecular pathologic markers were collected. Immunohistochemical staining of ASAP1 expression level were used to classify patients into high and low groups. In total, 452 cases low ASAP1 expression group was associated with significantly worse recurrence-free survival (p = 0.029). In ER-positive cases (n = 280), the low ASAP1 expression group was associated with significantly worse overall survival (p = 0.039) and recurrence-free survival (p = 0.029). In multivariate cox analysis, low ASAP1 expression was an independent significant predictor of poor recurrence-free survival in the overall patient group (hazard ratio = 2.566, p = 0.002) and ER-positive cases (hazard ratio = 4.046, p = 0.002). In the analysis of the TCGA dataset, the low-expression group of ASAP1 protein demonstrated a significantly poorer progression-free survival (p = 0.005). This study reports that low ASAP1 expression was associated with worse recurrence-free survival in invasive breast cancer.

Functional Analysis and Clinical Importance of ATP1A1 in Colon Cancer.

Na+/K+-ATPase α1 subunit (ATP1A1) exhibits aberrant expression in various types of cancer. Moreover, its levels in specific tissues are associated with the development of cancer. Nevertheless, the mechanism and signaling pathways underlying the effects of ATP1A1 in colon cancer (CC) have not been elucidated, and its prognostic impact remains unknown. Knockdown of ATP1A1 expression was performed in human CC cell lines HT29 and Caco2 using small interfering RNA. The roles of ATP1A1 in various biological processes of cells (i.e., proliferation, cell cycle, apoptosis, migration, and invasion) were assessed. Microarray analysis was utilized for gene expression profiling. Samples obtained from 200 patients with CC who underwent curative colectomy were analyzed through immunohistochemistry. ATP1A1 knockdown suppressed cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that the upregulated or downregulated gene expression in ATP1A1-depleted cells was related to the extracellular signal-regulated kinase 5 (ERK5) signaling pathway [epidermal growth factor receptor (EGFR), mitogen-activated protein kinase kinase 5 (MAP2K5), mitogen-activated protein kinase 7 (MAPK7), FOS, MYC, and BCL2 associated agonist of cell death (BAD)]. Immunohistochemical analysis demonstrated a correlation between ATP1A1 expression and pathological T stage (p = 0.0054), and multivariate analysis identified high ATP1A1 expression as an independent predictor of poor recurrence-free survival in patients with CC (p = 0.0040, hazard ratio: 2.807, 95% confidence interval 1.376-6.196). ATP1A1 regulates tumor progression through the ERK5 signaling pathway. High ATP1A1 expression is associated with poor long-term outcomes in patients with CC.

Pure Solid Pattern of Non-Small Cell Lung Cancer and Clustered Circulating Tumor Cells.

Simple SummaryThere are two solid patterns of non-small cell lung cancer (NSCLC) on computed tomography (CT): pure or mixed with ground glass opacities (GGOs). They predict the degree of tumor invasiveness, which may suggest the presence of clustered circulating tumor cells (CTCs), a predictor of poor prognosis. We assessed the implications of the solid patterns on CT and the preoperative clustered CTCs. Pure solid appearance was an independent predictor of preoperative clustered CTCs in the multivariable analysis, and preoperative clustered CTCs were an independent predictor of poor recurrence-free survival; the solid pattern was not an independent variable.There are two solid patterns of non-small cell lung cancer (NSCLC) on computed tomography (CT): pure or mixed with ground-glass opacities (GGOs). They predict the degree of invasiveness, which may suggest the presence of clustered circulating tumor cells (CTCs), a predictor of poor prognosis. In this study, we assessed the implications of the solid patterns on CT and the preoperative clustered CTCs in surgically resected NSCLC. CTCs were detected using a size selection method. The correlation between the presence of preoperative clustered CTCs and the solid pattern and the prognostic implications were evaluated using co-variables from the clinical-pathological findings. Of the 142 cases, pure solid lesions (Group PS) and mixed GGOs (Group G) were observed in 92 (64.8%) and 50 (35.2%) patients, respectively. In Groups PS and G, clustered CTCs were detected in 29 (31.5%) and 1 (2.0%) patient (p < 0.01), respectively. The PS appearance was an independent predictor of preoperative clustered CTCs in the multivariable analysis, and preoperative clustered CTCs were an independent predictor of poor recurrence-free survival; the solid pattern was not an independent variable. Thus, the PS pattern of NSCLC on CT is an indicator of preoperative clustered CTCs, which is an independent poor prognosis predictor.

Prognostic value of preoperative diabetes mellitus in patients with non-functional pancreatic neuroendocrine neoplasms

BackgroundThe main aim of this study was to investigate the prevalence and prognostic value of preoperative diabetes mellitus (DM) in patients with non-functional pancreatic neuroendocrine neoplasms (NF-PNENs). MethodsData were retrospectively collected from 190 patients with NF-PNENs from January 2009 to December 2019 in a single center. ResultsThe prevalence of longstanding DM, new-onset DM and impaired fasting glucose (IFG) was 11.6% (22/190), 8.4% (16/190), and 25.8% (49/190), respectively. Regression analysis showed that tumor size, tumor grade and lymph node metastasis were risk factors for new-onset DM and IFG. Multivariate survival analysis demonstrated preoperative new-onset DM (hazard ratio [HR], 4.33; P = 0.009) and IFG (HR, 4.53; P = 0.027) as independent predictors of poor recurrence-free survival (RFS) in patients with NF-PNENs. ConclusionPreoperative new-onset DM and IFG are associated with aggressive tumor behavior and poor RFS in patients with NF-PNENs.

Combined hepatocellular carcinoma-cholangiocarcinoma: MRI features correlated with tumor biomarkers and prognosis.

To determine how MRI features are correlated to biomarkers, and to the prognostic factors for recurrence-free survival (RFS) and overall survival (OS) in combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) patients. The study enrolled 160 cHCC-CCA patients pathologically confirmed according to the 2019 WHO classification. The preoperative MRI features and clinical data were retrospectively evaluated and compared between patients grouped by AFP or CA19-9 level and with pathological findings. The RFS and OS of cHCC-CCA patients were estimated using Kaplan-Meier survival curves and compared using the log-rank test. Moreover, predictors of RFS and OS were investigated using Cox regression analyses. One hundred and sixty patients (mean age, males vs. females: 55.7 ± 10.2 years vs. 54.9 ± 14.0 years) were evaluated. The incidence of nodule-in-nodule architecture, mosaic architecture, intratumoral hemorrhage, hepatic capsule retraction, arterial phase peritumoral enhancement, and portal vein thrombus was significantly higher in patients with AFP > 20 ng/ml (all p < 0.05). Multivariate Cox regression analysis indicated that age (HR 1.031, p = 0.03), CA19-9 > 37 U/ml (HR 1.880, p = 0.04), arterial phase peritumoral enhancement (HR 2.287, p = 0.01), and delayed enhancement (HR 0.377, p = 0.02) were independent predictors of poor RFS, while arterial phase peripheral enhancement (HR 2.391, p = 0.04) was an independent predictor of poor OS. cHCC-CCA imaging features are complex and not correlated with AFP or CA19-9. Age, CA19-9 > 37 U/ml, arterial phase peritumoral enhancement, and delayed enhancement are independent predictors of poor RFS. Arterial phase peripheral enhancement is an independent predictor of poor OS. • The imaging features of combined hepatocellular carcinoma-cholangiocarcinoma are complex and are not correlated with the alpha fetoprotein or CA19-9 levels. • Age, CA19-9 > 37 U/ml, arterial phase peritumoral enhancement, and delayed enhancement are independent predictors of poor recurrence-free survival in combined hepatocellular carcinoma-cholangiocarcinoma patients. • Arterial phase peripheral enhancement is an independent predictor of poor overall survival in patients with combined hepatocellular carcinoma-cholangiocarcinoma.

Cyclin-dependent kinase 9 (CDK9) predicts recurrence in Middle Eastern epithelial ovarian cancer

BackgroundCyclin-dependent kinase 9 (CDK9) has been shown to play an important role in tumorigenesis of several malignancies. However, the expression of CDK9 in ovarian cancer from Middle Eastern ethnicity remains unknown.MethodsA tissue microarray of 441 epithelial ovarian cancer (EOC) samples was used to study the expression of CDK9 immunohistochemically and their clinico-pathological associations were determined. Cox proportional hazards regression model was used for univariate and multivariate analysis of recurrence-free survival.ResultsCDK9 over-expression was noted in 56.2 % (248/441) of EOCs and was associated with adverse clinico-pathological parameters such as distant metastasis (p < 0.0001), stage IV tumors (p < 0.0001), tumor recurrence (p = 0.0105) and high Ki-67 index (p < 0.0001). Importantly, CDK9 over-expression was an independent predictor of poor recurrence-free survival (Hazard ratio = 1.51; 95 % confidence interval = 1.15–1.98; p = 0.0030). We also found that CDK9 outperforms Ki-67 as a predictor of tumor recurrence in EOC.ConclusionsOur results show that CDK9 expression correlates with markers of advanced disease in Middle Eastern EOC and is also a prognostic marker. CDK9 overexpression also identifies a subset of patients with highest likelihood of recurrence across the patient cohort. These patients may benefit from additional alternative therapies targeting CKD9.

Surgical outcomes of ipsilateral metachronous second primary lung cancer.

The optimal surgical approach for metachronous second primary lung cancer (MSPLC), especially ipsilateral MSPLC, remains unclear. This study aimed to review postoperative complications and examine surgical outcomes based on the extent of resection after surgery for ipsilateral MSPLC. Clinical data from 61 consecutive patients who underwent pulmonary resection for ipsilateral MSPLC according to the Martini-Melamed criteria between January 2005 and December 2017 in 3 institutes were retrospectively reviewed. Postoperative complications were identified in 12 patients (19.7%). Regarding the combination of initial and second surgery, intraoperative bleeding was significantly greater in patients with anatomic-anatomic resection than in others (P < 0.001). Operation time was significantly longer in patients with anatomic-anatomic resection than in others (P < 0.001). However, postoperative complications showed no significant differences based on the combination of surgeries. Five-year overall survival rates in patients with anatomic resection and wedge resection after second surgery were 75.8% and 75.8%, respectively (P = 0.738), and 5-year recurrence-free survival rates were 54.2% and 67.6%, respectively (P = 0.368). Cox multivariate analysis identified ever-smoker status (P = 0.029), poor performance status (P = 0.011) and tumour size >20 mm (P = 0.001) as independent predictors of poor overall survival, while ever-smoker status (P = 0.040) and tumour size >20 mm (P = 0.007) were considered independent predictors of poor recurrence-free survival. Regarding postoperative and long-term outcomes for patients with ipsilateral MSPLC, surgical intervention is safe and offers good long-term survival. Wedge resection is an acceptable provided tumours ≤2 cm and ground-glass opacity-predominant as a second surgery for early-stage ipsilateral MSPLC.

Overexpression of Epcam and CD133 Correlates with Poor Prognosis in Dual-phenotype Hepatocellular Carcinoma.

Background: Dual-phenotype hepatocellular carcinoma (DPHCC) is associated with high rate of post-operative recurrence and low rate of survival, which may reflect the post-operative persistence of cancer stem cells (CSCs). Here we explored the potential correlation between DPHCC and expression of CSCs markers.Methods: In this retrospective study, we included 19 patients with DPHCC and 61 patients with non-DPHCC treated in 2015 by liver resection. Paraffin-embedded tumor tissue specimens were analyzed using immunohistochemistry as well as immunofluorescence double-staining. Rates of recurrence-free survival and overall survival were compared between the two groups using the Kaplan-Meier method, and expression of the CSC markers CD133, CD90, and EpCAM were compared using real-time quantitative PCR and western blotting.Results: Overall survival rates were significantly lower for patients with DPHCC than patients with non-DPHCC at 1 year (78.9% vs 93.4%), 2 years (52.6% vs 72.1%), and 3 years (42.1% vs 67.2%) (P = 0.019). Multivariate Cox proportional hazard modeling identified CK19 positivity (P = 0.016) and multiple nodules (P = 0.023) as independent predictors of poor recurrence-free survival. Independent predictors of poor overall survival were CK19 positivity (P = 0.032), Barcelona Clinic Liver Cancer stage C (P = 0.025) and carbohydrate antigen 19-9 (CA19-9) >37 ng/ml (P = 0.016). Expression of CD133 and EpCAM mRNA and protein were significantly higher in DPHCC tissue than non-DPHCC tissue, while CD90 expression was similar between the groups.Conclusions: These results suggest that DPHCC is associated with significantly lower overall survival than non-DPHCC, and that the poor prognosis among DPHCC patients may be related to the presence of CSCs expressing CD133 and EpCAM.

Preoperative inflammatory response as prognostic factor of patients with colon cancer.

This study aimed to investigate the abilities of the modified Glasgow prognostic score (mGPS) and other inflammatory scores to predict recurrence-free survival (RFS) among patients with colon cancer (CC). In addition, we evaluated the abilities of the mGPS to predict recurrence of stage II disease and the efficacy of adjuvant chemotherapy (AC) for stage III disease. This retrospective study evaluated 477 patients with stage I-III CC who underwent curative surgery. These patients were categorized as having a low mGPS (mGPS 0) or a high mGPS (mGPS 1-2). Patients in the high mGPS group had significantly poorer RFS than patients in the low mGPS group (p < 0.01). Multivariate analysis revealed that a high mGPS independently predicted poor RFS (p < 0.01). Among patients with stage II CC, multivariate analysis revealed that the independent predictors of poor RFS were pT4 status (p < 0.01) and a high mGPS (p = 0.04). Among patients with stage III CC, AC was not significantly associated with the 5-year RFS for patients with a low mGPS (p = 0.38), although AC significantly improved the 5-year RFS for patients with a high mGPS (p < 0.01). The preoperative mGPS significantly predicted recurrence among patients with CC, even among patients with stage II CC. In addition, mGPS may provide valuable information regarding subgroups of patients with stage III CC who might benefit from AC.

Serum deprivation response functions as a tumor suppressor gene in papillary thyroid cancer.

The mechanism of papillary thyroid cancer (PTC) has shown numerous recurrently mutated genes, but the discovery of abnormal expression of novel tumor suppressor genes has been slow. The aim of our study is to explore the biological functions of SDPR in thyroid cancer. We reanalyzed the RNA-Seq data of PTC from The Cancer Genome Atlas (TCGA) database and found that serum deprivation response (SDPR) was significantly downregulated in PTC. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was performed to assess the expression of SDPR. Both loss- and gain-of-function experiments, and flow cytometry were performed to investigate the functions. SDPR was significantly downregulated in PTC. Reduced expression of SDPR was associated with larger tumor size, more serious lymph node metastasis, and advanced American Joint Committee on Cancer (AJCC) stage. Patients with lower SDPR expression had a shorter recurrence-free survival. SDPR expression and AJCC stage were independent predictors of poor recurrence-free survival (RFS). Moreover, cell proliferation, colony formation, and migration were inhibited after SDPR overexpression, whereas knockdown of SDPR exerted an oncogenic effect. SDPR induction also initiated the mesenchymal-epithelial transition, alongside suppressing AKT signaling and cyclin family expression. Apart from DNA methylation, LOC105373813, may also co-regulate SDPR expression by forming a stable hybrid with SDPR messenger RNA. Our study indicated that SDPR may function as a potential prognostic marker in PTC.

Does oesophageal stenosis have any impact on survival of oesophageal cancer patients?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'Does oesophageal stenosis have any impact on survival of oesophageal cancer patients?'. A total of 542 papers were found using the reported search, of which 8 cohort studies represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Most of these studies defined stenosis as failure to cross the tumour at endoscopic ultrasonography. Seven studies demonstrated that oesophageal cancer patients with stenosis had significantly poorer survival than those without, while 2 studies found that oesophageal stenosis was also a predictor of poor recurrence-free survival. We conclude that oesophageal stenosis is a predictor of poor prognosis in patients with oesophageal cancer.

Background parenchymal enhancement on breast MRI: association with recurrence-free survival in patients with newly diagnosed invasive breast cancer.

To determine whether BPE in preoperative breast MRI influences patients' recurrence-free survival (RFS). Between February 2010 and December 2011, 804 consecutive women with invasive breast cancer who had undergone preoperative breast MRI and curative cancer surgery were identified. BPE was visually graded by two reviewers. We determined the correlation between BPE grade and other clinicopathological variables, including age, adjuvant therapy, menopausal status, histologic grade, T stage, N stage, lymphovascular invasion, molecular subtype, surgical margin status, and mammographic density. A Cox proportional hazards model was used to analyze the effects of clinicopathological variables and radiological findings (BPE grade, mammographic density) on RFS. High BPE was associated with premenopausal status (Ps<0.0001), higher mammographic density (Ps<0.0001), progesterone receptor positivity (Ps=0.039, 0.007, respectively), presence of lymphovascular invasion (Ps=0.008, 0.001, respectively), and close surgical margin (Ps<0.0001). Recurrences were observed in 75 patients after a mean follow-up period of 61.8months (range 4-81months). Non-minimal BPE grade (RFS hazard ratio=3.086, P=0.003 for reader 1; RFS hazard ratio=2.221, P=0.075 for reader 2) and T3 stage were associated with worse outcomes in postmenopausal women. In premenopausal women, non-minimal BPE grade by readers 1 and 2 did not affect the patients' outcomes. Increased BPE on preoperative breast MRI in postmenopausal women has potential as a predictor of poor RFS.

Prognostic Value of Leptin Receptor Overexpression in Upper Tract Urothelial Carcinomas in Taiwan.

Leptin and its receptor (LEPR) are key players in the regulation of energy balance and body weight control and act as a growth factor for specific organs in both normal and disease states. However, LEPR accumulation may be involved in carcinogenesis, progression, and metastasis in many cancers. This study evaluated the clinical significance of LEPR expression in upper tract urothelial carcinoma (UTUC). LEPR expression was examined in 110 tissue samples from patients with UTUC, using immunohistochemistry, and an analysis was performed to identify evidence of association between LEPR expression and different clinicopathologic variables. LEPR expression was significantly correlated with patients with increased body mass index (P< .001) and high serum creatinine levels (P= .005). We found, using the log-rank test, that high LEPR expression was associated with poor recurrence-free (P= .009) and cancer-specific survival (P= .001). This finding was supported by our results using Cox regression analysis, which showed that LEPR expression was an independent predictor of poor recurrence-free survival (hazard ratio= 2.55; P= .011) and cancer-specific survival (hazard ratio= 2.26; P= .006). Our findings indicate that LEPR expression is a potential biomarker for predicting patient survival in UTUC. Further study is necessary to investigate the role of LEPR in carcinogenesis of UTUC.

Microscopic venous invasion in patients with pancreatic neuroendocrine tumor as a potential predictor of postoperative recurrence

BackgroundMicroscopic venous and lymphatic invasion is a known prognostic factor for various cancers, but its prognostic relevance for pancreatic neuroendocrine tumors (PNETs) is unclear. MethodsThirty-two consecutive patients with PNET who had complete resection were included in this study. Venous and lymphatic invasion was identified on elastic tissue or immunohistochemical staining, and correlated with other clinicopathological factors, including recurrence-free survival. ResultsVenous and lymphatic invasion was identified in nine (28%) and three (9%) patients, respectively. Tumors with venous invasion were of significantly larger size, higher Ki-67 index, and higher mitotic counts. Patients with venous invasion showed significantly worse prognosis than those without venous invasion (P = 0.001). Five of nine patients (56%) with venous invasion had tumor recurrence, while a relapse was found in one case in patients without venous invasion (n = 23). Lymphatic invasion was not correlated with any other clinicopathological parameters including lymph node metastasis and recurrence-free survival. Predictive factors for recurrence in univariate analysis included microscopic venous invasion, tumor size ≥ 20 mm, non-functionality, and WHO grades. In multivariate analysis where WHO grades and microscopic venous invasion were applied, venous invasion remained a significant predictor of poor recurrence-free survival (P = 0.021). ConclusionsMicroscopic venous invasion may serve as a predictive factor for tumor recurrence in patients with resectable PNET. The combination of WHO grades and microscopic venous invasion may assist in the stratification of the patients for risk of tumor recurrence.

Postoperative peak serum C-reactive protein is a predictor of outcome following liver transplantation for hepatocellular carcinoma

Context: C-reactive protein (CRP), a biomarker of inflammation, may correlate with prognosis in several malignancies.Objective: To investigate the prognostic impact of early postoperative peak serum levels of CRP on tumor-specific outcome in 106 liver transplant patients with hepatocellular carcinoma (HCC).Methods and results: In multivariate Cox regression analysis, a posttransplant elevated peak CRP level (>versus ≤ 3.5 mg/dl) was identified as an independent predictor of poor recurrence-free survival (p = 0.01; HR = 4.04; CI = 1.399–11.640).Conclusion: Early postoperative serum CRP may serve as a useful inflammation-based biomarker of outcome in liver transplant patients with HCC.

Prognostic impact of extent of vascular invasion in low-grade encapsulated follicular cell–derived thyroid carcinomas: a clinicopathologic study of 276 cases

Continuous controversy surrounds the predictive value of the degree of vascular invasion (VI) in low-grade encapsulated follicular cell-derived thyroid carcinomas (LGEFCs). Some guidelines advocate conservative therapy in LGEFCs with focal VI. There is therefore a need to assess the survival rates of LGEFC patients with various degrees of VI to better stratify patients for subsequent therapy. Furthermore, the prognostic effect of VI within the different histotypes of LGEFCs is not well known. A total of 276 patients with LGEFCs were subjected to a meticulous histopathologic analysis. They were classified as encapsulated papillary thyroid carcinoma, encapsulated follicular carcinoma (EFC), and encapsulated Hurthle cell carcinoma (EHCC). Of the 276 patients, 24 had extensive VI (EVI) (≥4 foci) and 28 displayed focal (<4 foci) VI. EHCC and EFC showed a much higher rate of EVI than encapsulated papillary thyroid carcinoma. Median follow-up was 6 years. All 14 tumors with adverse behavior harbored distant metastases (DMs), of which 9 had DMs at presentation. All 3 patients without EVI who had aggressive carcinomas harbored DMs at presentation. EVI was an independent predictor of poor recurrence-free survival. Excluding cases with DMs at presentation, only patients with EVI had recurrence, and all relapsed cases were EHCC. EVI is an independent predictor of recurrence-free survival in LGEFCs. EHCC with EVI has a particularly high risk of recurrence. When DMs are not found at presentation, patients with focal VI are at a very low risk of recurrence even if not treated with radioactive iodine.

P53 Status correlates with the risk of recurrence in non-muscle invasive bladder cancers treated with Bacillus Calmette-Guérin: a meta-analysis.

ObjectivePublished studies have yielded inconsistent results on the relationship between p53 status and the prognosis of non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette–Guérin (BCG) intravesical therapy. Therefore, we performed a meta-analysis to evaluate the prognostic value of p53 in NMIBC treated with BCG.MethodsWe systematically searched for relevant literature in PubMed, EMBASE, CNKI, and Chinese Wanfang databases. Hazard ratios (HRs) with 95% confidence intervals (CIs) were combined as the effect size (ES) across studies for recurrence-free survival (RFS) and progression-free survival (PFS).ResultsA total of 11 studies, consisting of 1,049 participants, met the criteria. Overall, there was no clear relationship between p53 status and RFS or PFS for NMIBC patients treated with BCG (HR: 1.40, 95% CI: 0.91-2.16; HR: 1.37, 95% CI: 0.90-2.09, respectively). Obvious heterogeneity was observed across the studies (I2 = 69.5%, P = 0.001; I2 = 44.7%, P = 0.081, respectively). In stratified analysis by region, p53 overexpression was a predictor of poor RFS in Asian populations (HR: 1.57, 95% CI: 1.08-2.27). In addition, after excluding the studies that possibly contributed to the heterogeneity by the Galbraith plot, the overall association for RFS became statistically significant (HR: 1.38 95% CI: 1.08-1.77) without evidence of heterogeneity (I2 = 0.0%, P = 0.499).ConclusionThis meta-analysis suggests that p53 overexpression in NMIBC patients treated with BCG may be associated with RFS, especially in Asian populations. Because of the heterogeneity and other limitations, further studies with rigid criteria and large populations are still warranted to confirm our findings.

Poor oncologic outcomes of hepatocellular carcinoma patients with intra-abdominal infection after hepatectomy.

To evaluate the impact of postoperative infectious complications on hepatocellular carcinoma following curative hepatectomy. We performed a retrospective analysis of 200 hepatocellular carcinoma patients who underwent hepatectomy at our institution between September 2003 and June 2011. The patients' demographics, clinicopathological characteristics and postoperative infectious complications were analyzed. The Clavien-Dindo classification was adopted to assess the severity of complications. The dynamic change in the neutrophil-to-lymphocyte ratio, defined as the absolute neutrophil count divided by the absolute lymphocyte count, after surgery was also investigated. The observation endpoints for this study were recurrence-free survival and overall survival of the patients. Statistical analysis of the survival curves was performed using the Kaplan-Meier method and the log-rank test. The prognostic value of each variable for predicting prognosis was assessed via multivariate Cox proportional hazards regression analysis. The cutoff score for each variable was selected based on receiver operating characteristic curve analysis. All statistical tests were two-sided, and significance was set at P < 0.05. The median age of the patients was 49 years, and the majority of patients were male (86%) and had been infected with hepatitis B virus (86%). The 30-d postoperative infectious complication rate was 34.0% (n = 68). Kaplan-Meier survival analysis revealed that postoperative infection was significantly correlated with tumor recurrence (P < 0.001). The postoperative intra-abdominal infection group exhibited a worse prognosis than the non-intra-abdominal infection group (P < 0.001). A significantly increased incidence of postoperative intra-abdominal infection was observed in the patients with hepatic cirrhosis (P = 0.028), concomitant splenectomy (P = 0.007) or vascular invasion (P = 0.026). The patients who had an elevated postoperative neutrophil-to-lymphocyte ratio change (> 1.643) clearly exhibited poorer recurrence-free survival than those who did not (P = 0.009), although no significant correlation was observed between overall survival and the change in the postoperative neutrophil-to-lymphocyte ratio. Based on multivariate analysis, hepatitis B surface antigen positivity, Child-Turcotte-Pugh class B, an elevated postoperative neutrophil-to-lymphocyte ratio change and intra-abdominal infection were significant predictors of poor recurrence-free survival. Hepatic cirrhosis, the maximal tumor diameter and intra-abdominal infection were significant predictors of overall survival. Postoperative intra-abdominal infection adversely affected oncologic outcomes, and the change in postoperative neutrophil-to-lymphocyte ratio was a good indicator of tumor recurrence in hepatocellular carcinoma patients after curative hepatectomy.

Tumor-associated CD66b+ neutrophil and CD8+ lymphocyte densities as independent prognostic factors for recurrence in localized cervical cancer: Automated digital image analysis and observer-assisted stereological assessments.

5532 Background: The prognostic impact of tumor-associated immune cells in cervical cancer is unclear. Methods: Automated digital image analysis (DIA) software and observer-assisted stereological (OAS) assessments were used to obtain densities of immunostains for CD66b+ neutrophils, CD163+ macrophages, and CD8+lymphocytes in scanned whole slide images of tumor sections from 101 patients with FIGO stage IB and IIA cervical cancer. Primary end-point was recurrence-free survival (RFS). Results: The highest densities of CD66b+ neutrophils and CD163+ macrophages were observed by OAS in the peritumoral compartment (median 53.1 cells/mm2 and 1.3% area fraction, respectively). DIA required far less human resources than OAS assessments. We observed high correlations between DIA and OAS variables of corresponding parameters; spearman ρ was 0.79 for CD8+ lymphocytes , 0.85 for CD66b+ neutrophils, and 0.92 for CD163+ macrophages (all p &lt;0.0001). Hazard rates for DIA assessments in the global tumor area were comparable with the prognostically strongest OAS assessments in the peritumoral compartment. In multivariate analysis, high density of CD66b+ neutrophils (HR 2.6; 95% CI 1.2–5.7; p = 0.02), low density of CD8+ lymphocytes (HR 2.3; 95% CI 1.1–4.9; p = 0.03), and presence of lymph node metastases (HR 2.6; 95% CI 1.2–5.5; p = 0.02) were independent predictors of poor RFS, whereas FIGO stage and CD163+macrophage density were not. The CD66b/CD8 immunostain index obtained by DIA had excellent discriminatory power for each quartile with 5-year RFS of 92%, 80%, 65%, and 48% for quartile I (&lt;0.019), II (0.02-0.05), III (0.06-0.24), and IV (&gt;0.25), respectively (p = 0.001). Conclusions: High tumor-associated CD66b+ neutrophil and low CD8+ lymphocyte densities are independent prognostic factors for short recurrence-free survival in cervical cancer assessed by DIA and OAS. Combined CD66b+ neutrophil/CD8+ lymphocyte immunostain index obtained by DIA is a strong and cost-efficient prognostic variable with potential for routine application.